Nicotinamide Riboside (NR): support for NAD⁺ metabolism and mitochondrial function
Within the biology of ageing, nicotinamide adenine dinucleotide (NAD⁺) plays a central role. NAD⁺ is an essential coenzyme for mitochondrial energy production, DNA repair processes, and the regulation of cellular stress responses. With advancing age, NAD⁺ levels decline in various tissues, which is linked to reduced cellular energy balance, diminished repair capacity, and increased inflammatory activity—processes associated with several so-called Hallmarks of Aging.¹
Nicotinamide Riboside (NR) is one of the most thoroughly studied precursors of NAD⁺. After oral intake, NR is converted through specific enzyme pathways (NRK1 and NRK2) into nicotinamide mononucleotide (NMN) and then into NAD⁺. This can increase the available intracellular NAD⁺ pool, which forms the biochemical basis for supporting energy and repair processes.²
Human clinical studies show that oral NR supplementation effectively raises NAD⁺ status in people and is generally well tolerated. In a randomized, placebo-controlled study in healthy middle-aged and older adults, six weeks of NR supplementation led to a significant rise in NAD⁺ metabolites in the blood.³ Other clinical studies confirm that repeated daily doses of NR over several weeks increase blood NAD⁺ levels, without serious side effects.⁴
In addition, an early human pharmacokinetic study showed that even a single oral dose of NR can lead to a substantial increase in the concentration of NAD⁺ in the blood, supporting the biochemical availability of NR in humans.²
Furthermore, human data suggest that NR supplementation in older adults can increase the NAD⁺ metabolome in skeletal muscle and is associated with changes in gene expression and signalling pathways involved in inflammation and mitochondrial function.⁵
Taken together, these findings show that Nicotinamide Riboside is among the best-substantiated NAD⁺ precursors currently available. The scientific literature consistently supports that NR increases NAD⁺ status in humans, which is an important biochemical condition for the functioning of cellular energy and repair mechanisms during ageing.
Sources (complete and checked)
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Science Advances (2023)
Review article on NAD⁺ metabolism, ageing, oxidative stress, and inflammation.
https://www.science.org/doi/10.1126/sciadv.adi4862 -
Trammell SAJ et al. (2016)
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.
Nature Communications, 7:12948.
https://doi.org/10.1038/ncomms12948 -
Martens CR et al. (2018)
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD⁺ in healthy middle-aged and older adults.
Nature Communications, 9:1286.
https://doi.org/10.1038/s41467-018-03421-7 -
Vreones M et al. (2023)
Oral nicotinamide riboside raises NAD⁺ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin.
Aging Cell, 22(1):e13754.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9835564/ -
Elhassan YS et al. (2019)
Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD⁺ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Reports, 28(7):1717–1728.e6. https://doi.org/10.1016/j.celrep.2019.07.043
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